Reduction of ethanol-derived acetaldehyde induced motivational properties by L-cysteine.
BACKGROUND
Experimental evidences suggest that acetaldehyde (ACD) contributes to the positive motivational properties of ethanol (EtOH) as assessed by the place conditioning paradigm; indeed, we found that by reducing ACD production and/or by using ACD-sequestrating agents, EtOH is deprived from its motivational properties. Thiol products, such as the amino acid cysteine, are known to be effective ACD-sequestering agents. Cysteine is able to covalently bind ACD thereby forming a stable, nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, we treated rats with l-cysteine before intragastric administration of EtOH or ACD.


METHODS
Male Wistar rats were pretreated intraperitoneally with saline or l-cysteine (10, 20, or 30 mg/kg), before intragastric administration of saline, EtOH (1 g/kg), or ACD (20 mg/kg). The specificity of l-cysteine effect was addressed using morphine-induced conditioned place preference (cpp) (2.5 mg/kg, i.p.).


RESULTS
l-cysteine dose-dependently prevented both EtOH and ACD-induced cpp but did not interfere with morphine-induced cpp, suggesting that l-cysteine specifically modulates the motivational properties of EtOH.


CONCLUSIONS
The present results further underscore the role of EtOH-derived ACD in EtOH-induced motivational properties. l-cysteine, by binding EtOH-derived ACD, would deprive it of its rewarding properties and reduce its abuse liability.
Peana
Alessandra T
AT
G. Minardi Laboratory of Cognitive Neuroscience, Department of Drug Sciences, University of Sassari, Sassari, Italy. apeana@uniss.it
Assaretti
Anna Rita
AR
Muggironi
Giulia
G
Enrico
Paolo
P
Diana
Marco
M
D000079:Acetaldehyde / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003545:Cysteine / Q000008:administration & dosage* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D009042:Motivation; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D000079:Acetaldehyde; D003545:Cysteine